A double-blind RCT of 210 patients undergoing Mohs micrographic surgery for head and neck skin cancers compared paracetamol 1000 mg, paracetamol/ibuprofen 1000/400 mg, and paracetamol 325 mg plus 30 mg codeine immediately after surgery and every 4 hours for up to four doses.10
The paracetamol/ibuprofen group had the lowest pain scores (change from baseline in VAS) at each postoperative recorded time interval and a significantly smaller change from preoperative pain scores than the paracetamol/codeine group at 4 hours (p = 0.005) and the paracetamol group at 8 hours (p = 0.02). The paracetamol/codeine group had the highest complication rate, mainly due to adverse GI effects.10
A 2012 double-blind RCT compared the efficacy of up to 7 days’ treatment with paracetamol/ibuprofen 650/400 mg with a fixed-dose combination of paracetamol 600 mg, codeine 60 mg and caffeine 30 mg (Tylenol 3) after outpatient breast surgery.11
The paracetamol/ibuprofen combination provided at least as effective analgesia as its codeine-based comparator, with fewer discontinuations due to adverse effects.11
In the dental pain model, a double-blind single-dose RCT compared one or two tablets of paracetamol/ibuprofen 500/200 mg with two tablets of ibuprofen/codeine 200/12.8 mg (Nurofen Plus), two tablets of paracetamol/codeine 500/15 mg (Panadeine Extra), or placebo.4,12
Both the one- and two-tablet combinations of paracetamol/ibuprofen were significantly more efficaciousb than paracetamol/codeine (p ≤ 0.0001). Two tablets offered significantly greater pain relief than ibuprofen/codeine (p = 0.0001), with one tablet found to be non-inferior to this combination.
Adverse events were less frequent in the groups taking the paracetamol/ibuprofen combination compared with the codeine combinations.4,12
b The primary efficacy endpoint was the sum of mean scores of pain relief combined with pain intensity differences over 12 hours.